Do interictal spikes sustain seizures and epileptogenesis?

Abstract

Interictal spiking is seen in the EEG of epileptic patients between seizures. To date, the roles played by interictal events in seizure occurrence and in epileptogenesis remain elusive. While interictal spikes may herald the onset of electrographic seizures, experimental data indicate that hippocampus-driven interictal events prevent seizure precipitation. Even less clear than the role of interictal events in seizure occurrence is whether and how interictal spikes contribute to epileptogenesis. Thus, while plastic changes within limbic neuronal networks may result from ongoing interictal activity, experimental evidence supports the view that epileptogenesis is accompanied by a decrease in hippocampus-driven interictal activity.

FIGURE 1

A: Spontaneous epileptiform activity recorded at hour 1 and 2 during continuous bath application of 4-AP. Simultaneous field potential recordings were made in the CA3 stratum radiatum, the deep layers of the EC, and the DG cell layer. The interictal discharges recorded at 1 hour are indicated by arrows; note that after 2 hours of 4-AP application, ictal discharges disappear. Adapted with permission from J Neurosci. (10) Copyright 1997 Society for Neuroscience. B: Expanded traces of interictal (a) and ictal discharges (b) induced by 4-AP (∼1 hour) in an intact EC–hippocampal combined slice. In a, the interictal discharge initiates in the CA3 region and propagates to the EC and DG; arrows point to the late components of the interictal discharge recorded in CA3. In b, the ictal discharge is preceded by an interictal event, with a temporal profile similar to that seen in a; note, however, that the site of origin of the ictal discharge occurs in EC. Dotted lines in a and b were positioned at the time of the earliest visible deflection in the three-field potential recordings. Adapted with permission from J Neurosci. (10) Copyright 1997 Society for Neuroscience. C: Effect of cutting the Schaffer collaterals on 4-AP-induced epileptiform discharges. Field recordings were obtained in an intact EC–hippocampal slice after ictal discharges have stopped occurring (upper panel) and after Schaffer collateral cut (lower panel); note that this procedure makes CA3-driven interictal events disappear in EC, while ictal discharges remain unabated. Adapted with permission from J Neurophysiol. (46) Copyright 2000 American Physiological Society. EC, entorhinal cortex; DG, dentate granule; 4-AP, 4-aminopyridine.

FIGURE 2

A and B: Field and intracellular (potassium-acetate–filled microelectrode) recordings from the EC demonstrate two types of activity during 4-AP application. Slow interictal and ictal discharges are identified with asterisks and an open circle, respectively. Note the similarities between the isolated interictal discharge (Ba) and the onset of the ictal event (Bb). Adapted with permission from J Neurophysiol. (47) Copyright 1998 American Physiological Society. C: When the neuronal membrane is depolarized by intracellular injection of steady positive current (−55 mV), the amplitude of sustained ictal depolarization decreases, while the initial long-lasting depolarization becomes hyperpolarizing as compared with the recording obtained at resting membrane potential (−70 mV). When the membrane is hyperpolarized by intracellular injection of steady negative current (−80 mV) both long-lasting depolarization and ictal depolarization increase in amplitude as compared with the samples obtained at resting membrane potential. The time occupied by this initial long-lasting depolarization is indicated by the continuous line on top of the −55 mV trace. Adapted with permission from J Neurophysiol. (47) Copyright 1998 American Physiological Society. EC, entorhinal cortex; DG, dentate granule; 4-AP, 4-aminopyridine.